At present, the overall success rate for in vitro fertilization is approximately 20-25%. This figure includes multiple attempts (up to 3-4 times by some couples) to succeed. Thus, any process which can increase the efficiency of fertilization will have significant utility for in vitro fertilization procedures.
On the other hand, it is estimated that there are 1.5 to 2 million pregnancies that occur in the United States alone because of failures in contraception. Failure rates of vaginal contraceptives such as foam or jelly, either alone or in combination with condoms or diaphragm, range from 2-20% per year depending on conditions and the study cited. See Developing New Contraceptive: Obstacles and Opportunities, Washington D.C., National Academy Press (1990). Therefore, any minor improvement in the efficiency of contraceptives, thousands of accidental or unwanted pregnancies could be prevented per year.
Bombesin, a tetradecapeptide amide first isolated from the skin of the frog Bombina bombina, is a potent mitogen for mouse Swiss 3T3 fibroblast cells. It also stimulates secretion for guinea pig pancreatic acini. Bombesin-like peptides are produced and secreted by human small cell lung cancer cells ("SCLC") and exogenously added bombesin-like peptides can stimulate the growth of human SCLC cells in vitro. Two examples of bombesin-like peptides are gastrin releasing peptide ("GRP") and Neuromedin C.
GRP is a 27 amino acid peptide amide first isolated from the porcine gut. The C-terminal amino acid sequence of GRP is almost identical to that of bombesin. Neuromedin C is a decapeptide amide, the structure of which is identical to the last ten amino acids in the C-terminal region of GRP. Both GRP and Neuromedin C share amino acid sequence homology with bombesin and possess bombesin-like properties. Other bombesin-like peptides include litorin and Neuromedin B.
GRP is encoded by a gene located on the 18th chromosome. Naylor et al. Somat. Cell Mol. Genet. 13:87 (1987). GRP is encoded by 3 exons with exon 1 encoding the first 23 amino acids of GRP and exon 2 the latter 4 amino acids. Spindel et al. Mol. Endocrinol. 1:224 (1987). The GRP prohormone includes a signal peptide, the sequence of GRP, a dibasic amino acid cleavage site, and a long C-terminal peptide following the cleavage site. Bioactive GRP is processed from the prohormone basically in 3 steps; first by removal of the signal peptide, second by cleavage of the C-terminal peptide at the dibasic site, and third by amidation of GRP. GRP itself may then be further cleaved to give the C-terminal decapeptide of GRP (GRP-10) which has similar bioactivity as does GRP.
For fertilization to occur, sperm must undergo an exocytotic process called the acrosome reaction which enables sperm to penetrate the external layers of the ova. It has not been reported hitherto that bombesin or bombesin-like peptides are capable of increasing or decreasing the efficiency of fertilization of eggs by sperm by promoting acrosome reaction.